The basic function of the skin is to create a barrier which can protect the body against environmental damages and effects, and to ensure homeostasis. Thus, any deformation that may occur in the skin integrity may leave the human body vulnerable against many pathological situations such as infection, extreme dehydration, electrolyte imbalance, etc. (Baum and Arpey, 2005). For this reason, large damages that may occur on the skin due to diseases or injuries cause serious dysfunctions and even deaths (Singer and Clark, 1999). Immediately after impairment of skin integrity, wound healing starts in the body. This is a complex event where a series of biological events regularly follow each other, and it mostly ends up with partial or complete regeneration of the tissue. Generally, wound healing is comprised of four interconnected phases which are homeostasis, inflammation, proliferation and remodeling (Diegelmann and Evans, 2004). Even though the organism is organized to close and remodel the wound, many factors independent of the organism may delay the process by affecting wound healing and cause formation of chronic wounds. For example, microbial, contamination that may occur at the wound area and the products (endotoxin, metalloproteinase, etc.) formed by these microorganisms may impede restoring skin integrity by affecting the healing process negatively (Robson, 1997). As the microbial colonization forming on the wound surface is a poly-microbial environment accommodating many pathogens, the risk of infection of the wound is high (Bowler et al., 2001). Infection of the wound delays wound healing and cause the trauma to increase, and the treatment processes to be more complex and costly.
Zoutman et al. have shown with the study they have conducted that wound infection increases length of hospitalization of the patient averagely by 10.2 days and that this brings an additional cost of $3,937 per patient (1998).
In order to prevent contamination of the wound area by any microorganism, the immune system cells stimulated by growth factor and cytokines migrate to the wound area. In the inflammation step which takes place right after the wound occurs, neutrophils and macrophages arrive at the wound area. In addition to these, lymphocytes and monocytes also go to the wound area, transform into macrophages and help the defense system. The neutrophils and macrophages that have reached the wound area inhibit the microorganisms at the wound area by producing a high amount of reactive oxygen species (ROS) (Gordillo and Sen, 2003). If there is extreme microbial contamination in the wound area, neutrophil and macrophage densities increase and these cells, which produce excessive amounts of ROS, cause tissue and cell destruction. This destruction delays wound healing. The reactive oxygen species interact with DNA, protein and lipids and cause degradation of them. The ROS species bind to DNA and cause double or single strand breakdowns and mutations (Bartosz, 2008). In addition to that, they cause lysis of the cells by causing ROS lipid peroxidation (Panchatcharam et al., 2006). Another example of negative impacts of ROS species on wound healing is the fact that ROS species such as hydrogen peroxide reduce proliferation and migration of many cells such as keratinocytes (O'Toole et al. 1996). However certain adaptations have developed against ROS species in order to maintain skin integrity. ROS detoxification is provided by two different strategies in the cell. ROS is eliminated by small antioxidant molecules such as Poly-unsaturated fatty acid, ascorbate or sugars (mostly mannitol) or with superoxide dismutase (SOD), catalase and various peroxidases (e.g. glutathione peroxidase) (Steiling et ah, 1999). Among these enzymes, superoxide dismutase (SOD) enables transformation of superoxide radical anion, which is mostly formed in the wound healing process, to hydrogen peroxide (Ulrich et al., 2006). Even though hydrogen peroxide is not radical, it should be immediately decomposed because of its capacity of transforming to hydroxyl radical. Reaction of reducing hydrogen peroxide to water is generally performed with the help of catalase and glutathione enzymes. During wound healing, if the amount of these enzymes is less than that of ROS species, they cause DNA damage, protein and lipid peroxidation at the wound area and thus delay wound healing.
Cellular communication, extracellular matrix (ECM) formation, growth factors and cytokine release should be complete for a complete healing in the process of wound healing. ECM formation is included almost in the entire wound healing process and has an important place. Generally, the components forming ECM are synthesized and combined outside of the cell surface and thus provide structural and functional integrity to connective tissues and organs. ECM synthesis and storing out of the cell are enabled by the signal, transmission means, growth factors and cytokine release provided by means of cell surface receptors (Schultz and Wysocki, 2009). Fibroblast cells synthesize various collagen types right after wound formation in order to recover the damage that has occurred in the tissue and to maintain integrity (McPherson and Piez, 1988). Collagen type 1 and 3 provide tensile strength of the skin and thereby enable the skin to be strong and resistant against mechanical stress.
At first, collagen was thought to be necessary only for maintaining skin integrity, however new studies have shown that collagen is also important for synthesis of many proteins required for the cell form and differentiation, migration and wound healing (Brett, 2008). In order to ensure an effective migration of keratinocytes, there must be sufficient amount of collagen type 1 at the wound area.
Another important extracellular matrix protein is fibronectin. Fibronectin, which is an adhesive glycoprotein synthesized by the cells at the wound area, serves for cell adhesion, growth, cell migration and differentiation. Fibronectin acts as a biological adhesive due to its molecular structure and functions as an important bridge for the cell to communicate with the other extracellular matrix proteins (Clark, 1990). Fibronectin and fibrin enable cell adhesion and migration by producing a temporary matrix at the wound area. However when dermalepidermal regeneration is completed, fibronectin mostly remains limited with the basal membrane region of the dermal-epidermal connection region (Schultz and Wysocki, 2009). Thus, fibronectin has effects that vary according to certain steps of wound healing.
Increase of remodeling and synthesis of ECM also delays aging on the skin. As the ECM layer on the aging skin becomes more fragile, wrinkles occur. The skin composition which has aged due to internal or external factors may have been caused by a reduction of the amount or a deformation of ECM in the dermis layer (Takasao et al., 2012). Thus, induction of collagen type 1, which constitutes 90% of ECM composition in the dermis layer, and elastic fiber synthesis enables the skin to stay young by slowing down aging (Fernandes and Signorini, 2012).
Not only ECM deficiency but also ROS redundancy plays a large role in aging. ROS, occurring due to environmental conditions, causes increase (up-regulation) of the matrix metalloproteinases that particularly serve for ECM destruction by increasing inflammation on the skin (Pillai et al., 2005). In addition to causing inflammation, ROS derivatives result, in damages on the skin surface by causing protein carbonylation and lipid peroxidation (Masaki, 2010). For these reasons, since increasing the activities of the enzymes (e.g. SOD, glutathione peroxidase and catalase) serving for ROS elimination will reduce the breakdowns that might occur in the skin, it will slow down aging.
Although boron is an important trace element for plants, its activity and mechanism on mammalian system has not been completely understood. In several studies conducted up to date, it is claimed that several compounds containing boron can be effective in the process of wound healing It was observed that topical administration of 3% boric acid on wounds reduced length of stay in intensive care units by three times (Nzietchueng et al., 2002). Additionally, it has been, shown in in vitro studies that boric acid increases extracellular matrix proteins (Benderdour et al., 1998). It was claimed that boric acid reduces synthesis of intracellular molecules (proteoglycan, collagen and proteins) and increases release of these molecules to culture medium (Benderdour et al., 1997). Apart from this, although it was found that four different compounds (triethanolamine borate; N-diethyl-phosphoramidate-propylboronique acid; 2,2 dimethylhexyl-1,3-propanediol-aminopropylboronate and 1,2 propanediolaminopropyl-boronate) which are boron derivatives provide more extracellular matrix protein than boric acid, it was also stated that these compounds are more toxic than boric acid (Benderdour et al., 2000).
It was shown in the in vitro studies that were conducted that sodium borate compound, which is another boron compound, increases cell migration although it does not have proliferative effect on human keratinocytes (Chebassier et al., 2004a) and increases the levels of metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) enzymes which serve for dermal cell migration and granulation tissue modeling which are important steps in wound healing process (Chebassier et al., 2004b).
Poloxamers are synthetic polymers which have a triblock structure composed of hydrophobic polypropylene oxide and hydrophilic polyethylene oxide units. Poloxamer can be used for carrying therapeutic agents, drugs and genes (Batrokova and Kabanov, 2008). Due to their amphophilic structures, they serve as surfactants and can interact with membranes. In solutions, they can absorb drags and can be used for carrying thereof by forming micelle at concentrations above critical micelle concentration (Kabanov et al., 1995). They can be used in bioreactors for enhancing cell viability and decreasing agitation stress (Ramirez and Mutharasan, 1990).
The United States patent document numbered US2010286010, one of the applications known in the art, discloses an aqueous solution for cleaning and disinfecting contact lenses.